<font class="mainfont">I am a postdoctoral fellow in the [[kafatos:Kafatos/Christophides Lab|Kafatos/Christophides lab]] at [http://www.imperial.ac.uk/ Imperial College London]. My research focuses on how the innate immune system of the mosquito recognizes and eliminates malaria parasites. Widely considered to be passive carriers of malaria, mosquitoes are actually amazing parasite killers. In fact, the vast majority of the parasites ingested when a mosquito bites a malarious person are attacked and eliminated before they can mount an infection. It is the few parasites that survive (even one is sufficient), that are ultimately responsible for disease transmission.

The mosquito has multiple lines of defense against invading pathogens, but the most potent is found in its blood, called hemolymph. Parasites migrate through the gut epithelium in order to escape the harsh digestive conditions of the gut lumen. Here they come into contact with the hemolymph. Two leucine-rich repeat (LRR) containing proteins, LRIM1 and APL1C, are essential for mosquito immune defense in this compartment. These proteins circulate in the mosquito hemolymph in a disulfide-bonded dimer (Povelones 2009). If either LRIM1 or APL1C is knocked-down by RNAi, the complex is undetectable in the hemolymph and parasite survival is massively increased. Before parasites are killed, the complement-like protein TEP1 is localized on their surface, marking them for destruction. The LRIM1/APL1C complex physically interacts with a proteolytically processed and highly reactive form of TEP1. The interaction stabilizes TEP1 in the hemolymph and is required for its localization to parasites during midgut invasion. When the LRIM1/APL1C complex is knocked-down, TEP1 fails to localize and the invading parasites are not killed. This immune pathway leading to parasite killing could be an important cause of natural refractoriness in non-vector mosquitoes (Habtewold, 2008). We recently discovered that the LRIM1/APL1C complex can also interact with 3 other members of the TEP family. Two of these were previously characterized to contribute to mosquito antibacterial defense reactions. We found that one of these, TEP3, also functions in mosquito immune reactions against parasites (Povelones, 2011). Understanding the mechanism of parasite killing, and how some parasites manage to escape, may open the door to novel control strategies.

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===Previous Research===

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Additionally, we have found that LRIM1 and APL1C are defining members of a protein family, collectively named LRIMs (pronounced L-rims) (Povelones, 2009; Waterhouse 2010). Bioinformatic searches using specific features shared between LRIM1 and APL1C has uncovered approximately 20 family members falling into four distinct sub-families in the mosquito species ''Anopheles gambiae'', ''Aedes aegypti'' and ''Culex quinquefasciatus''. This family is not found in any other organism. Given the central role of LRR proteins in host defense in plants and animals, we are currently investigating the hypothesis that the repertoire of LRIMs may help the mosquito neutralize diverse pathogens, including the agents of human and animal diseases that they transmit. </font>

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<font size="3">I received my doctoral degree at Stanford University in the laboratory of Roel Nusse. The focus of my research was understanding how the ''frizzled (fz)'' receptor in ''Drosophila'' functions in planar cell polarization (PCP) and Wnt-mediated cell fate specification. ''fz'' controls two different signal transduction pathways for each of these distinct developmental outcomes. How does a single receptor function in two signaling pathways? This work revealed that even though cell fate signaling requires a Wnt ligand, ''fz'' is not activated by any of the 7 ''Drosophila'' Wnt genes for its PCP function. Instead, ''fz'' has an intrinsic ability to control components of the PCP pathway and that it associates with pathway specific Wnt co-receptor for cell fate signaling. In addition, a structure-function analysis of ''fz'' suggested that, in addition to the Wnt binding site located in the extracellular cysteine-rich domain, there is a second Wnt-binding site within the transmembrane portion of the receptor.</font>

<font size="3">I worked in the laboratory of Richard Ambron as an undergraduate at Columbia University. The focus of this research was the identification of intrinsic nerve injury signals. In addition to growth factor and electrophysiological responses, neurons posses axonal proteins with a masked nuclear localization sequence (NLS) that serve as a sensor for injury. These injury signals are activated and rapidly retrogradely transported to the neuronal cell body and into the nucleus following nerve crush injury. In the nucleus they function to initiate the transcriptional program for repair. My research focused on the identification of an NF-&kappa;B-like transcription factor in Aplysia and its function in nerve injury. Nerve regeneration following injury requires transcriptional activation of repair genes. Members NF-&kappa;B family of transcription factors are well-suited to play a role in nerve injury since they contain and masked NLS and are localized to the cytoplasm until activated. This work identified by electrophoretic mobility shift assay an NF-&kappa;B-like activity in axoplasm. Contrary to what was expected, this activity was rapidly inactivated in injured neurons. We hypothesized that in these neurons, NF-&kappa;B functions as a signal of homeostasis and must be inactivated following injury since it regulates genes that are incompatible with repair. </font>

Current Research Interests

I am a postdoctoral fellow in the Kafatos/Christophides lab at Imperial College London. My research focuses on how the innate immune system of the mosquito recognizes and eliminates malaria parasites. Widely considered to be passive carriers of malaria, mosquitoes are actually amazing parasite killers. In fact, the vast majority of the parasites ingested when a mosquito bites a malarious person are attacked and eliminated before they can mount an infection. It is the few parasites that survive (even one is sufficient), that are ultimately responsible for disease transmission.

The mosquito has multiple lines of defense against invading pathogens, but the most potent is found in its blood, called hemolymph. Parasites migrate through the gut epithelium in order to escape the harsh digestive conditions of the gut lumen. Here they come into contact with the hemolymph. Two leucine-rich repeat (LRR) containing proteins, LRIM1 and APL1C, are essential for mosquito immune defense in this compartment. These proteins circulate in the mosquito hemolymph in a disulfide-bonded dimer (Povelones 2009). If either LRIM1 or APL1C is knocked-down by RNAi, the complex is undetectable in the hemolymph and parasite survival is massively increased. Before parasites are killed, the complement-like protein TEP1 is localized on their surface, marking them for destruction. The LRIM1/APL1C complex physically interacts with a proteolytically processed and highly reactive form of TEP1. The interaction stabilizes TEP1 in the hemolymph and is required for its localization to parasites during midgut invasion. When the LRIM1/APL1C complex is knocked-down, TEP1 fails to localize and the invading parasites are not killed. This immune pathway leading to parasite killing could be an important cause of natural refractoriness in non-vector mosquitoes (Habtewold, 2008). We recently discovered that the LRIM1/APL1C complex can also interact with 3 other members of the TEP family. Two of these were previously characterized to contribute to mosquito antibacterial defense reactions. We found that one of these, TEP3, also functions in mosquito immune reactions against parasites (Povelones, 2011). Understanding the mechanism of parasite killing, and how some parasites manage to escape, may open the door to novel control strategies.

Additionally, we have found that LRIM1 and APL1C are defining members of a protein family, collectively named LRIMs (pronounced L-rims) (Povelones, 2009; Waterhouse 2010). Bioinformatic searches using specific features shared between LRIM1 and APL1C has uncovered approximately 20 family members falling into four distinct sub-families in the mosquito species Anopheles gambiae, Aedes aegypti and Culex quinquefasciatus. This family is not found in any other organism. Given the central role of LRR proteins in host defense in plants and animals, we are currently investigating the hypothesis that the repertoire of LRIMs may help the mosquito neutralize diverse pathogens, including the agents of human and animal diseases that they transmit.